A human genome editing-based MLL::AF4 ALL model recapitulates key cellular and molecular leukemogenic features

Clara Bueno^{1

2

3}, Raul Torres-Ruiz^{1

4

5

6

7}, Talia Velasco-Hernandez^{1

2}, Oscar Molina^{1

2}, Paolo Petazzi¹, Alba Martinez^{1

2}, Virginia Rodriguez^{1

2}, Meritxell Vinyoles^{1

2}, Sandra Cantilena⁸, Owen Williams⁸, Nerea Vega-Garcia^{9

10}, Sandra Rodriguez-Perales⁷, Jose C Segovia^{4

5

6}, Oscar Quintana-Bustamante^{4

5

6}, Anindita Roy^{11

12}, Claus Meyer¹³, Rolf Marschalek¹³, Alastair L Smith¹¹, Thomas A Milne¹¹, Mario F Fraga^{6

14

15}, Juan Ramón Tejedor^{6

14

15}, Pablo Menéndez^{1

2

3

16

17}

Affiliations

¹ Stem Cell Biology, Immunotherapy and Developmental Leukemia Laboratory. Josep Carreras Leukemia Research Institute, Barcelona, Spain.
² Spanish Network for Advanced Therapies, Carlos III Health Institute, Barcelona, Spain.
³ Spanish Collaborative Cancer Network, Carlos III Health Institute, Barcelona, Spain.
⁴ Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain.
⁵ Advanced Therapies Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain.
⁶ Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
⁷ Molecular Cytogenetics and Genome Editing Unit, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain.
⁸ Development Biology Cancer Program, Cancer Section, UCLGOS Institute of Child Health, London, United Kingdom.
⁹ Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain.
¹⁰ Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona, Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain.
¹¹ MRC Molecular Hematology Unit, MRC Weatherall Institute of Molecular Medicine, Oxford Biomedical Research Center Hematology Theme, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
¹² Department of Pediatrics and National Institute for Health and Care Research Oxford Biomedical Research Centre Hematology Theme, University of Oxford, Oxford, United Kingdom.
¹³ Diagnostic Center of Acute Leukemia-Institute of Pharmaceutical Biology, Goethe-University, Frankfurt/Main, Germany.
¹⁴ Cancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center, El Entrego, Spain.
¹⁵ Health Research Institute of Asturias, Institute of Oncology of Asturias and Department of Organisms and Systems Biology, University of Oviedo, Oviedo, Spain.
¹⁶ Department of Biomedicine, University of Barcelona, Barcelona, Spain.
¹⁷ Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.

PMID: 37756522
DOI: 10.1182/blood.2023020858

Free article

A human genome editing-based MLL::AF4 ALL model recapitulates key cellular and molecular leukemogenic features

Clara Bueno et al. Blood. 2023.

Free article

. 2023 Nov 16;142(20):1752-1756.

doi: 10.1182/blood.2023020858.

Authors

Affiliations

¹ Stem Cell Biology, Immunotherapy and Developmental Leukemia Laboratory. Josep Carreras Leukemia Research Institute, Barcelona, Spain.
² Spanish Network for Advanced Therapies, Carlos III Health Institute, Barcelona, Spain.
³ Spanish Collaborative Cancer Network, Carlos III Health Institute, Barcelona, Spain.
⁴ Division of Hematopoietic Innovative Therapies, Biomedical Innovation Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain.
⁵ Advanced Therapies Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain.
⁶ Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
⁷ Molecular Cytogenetics and Genome Editing Unit, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain.
⁸ Development Biology Cancer Program, Cancer Section, UCLGOS Institute of Child Health, London, United Kingdom.
⁹ Hematology Laboratory, Hospital Sant Joan de Déu Barcelona, Barcelona, Spain.
¹⁰ Developmental Tumors Biology Group, Leukemia, and other Pediatric Hemopathies, Pediatric Cancer Center Barcelona, Institut de Recerca, Hospital Sant Joan de Déu, Barcelona, Spain.
¹¹ MRC Molecular Hematology Unit, MRC Weatherall Institute of Molecular Medicine, Oxford Biomedical Research Center Hematology Theme, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
¹² Department of Pediatrics and National Institute for Health and Care Research Oxford Biomedical Research Centre Hematology Theme, University of Oxford, Oxford, United Kingdom.
¹³ Diagnostic Center of Acute Leukemia-Institute of Pharmaceutical Biology, Goethe-University, Frankfurt/Main, Germany.
¹⁴ Cancer Epigenetics and Nanomedicine Laboratory, Nanomaterials and Nanotechnology Research Center, El Entrego, Spain.
¹⁵ Health Research Institute of Asturias, Institute of Oncology of Asturias and Department of Organisms and Systems Biology, University of Oviedo, Oviedo, Spain.
¹⁶ Department of Biomedicine, University of Barcelona, Barcelona, Spain.
¹⁷ Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.

PMID: 37756522
DOI: 10.1182/blood.2023020858

Abstract

Cellular ontogeny and MLL breakpoint site influence the capacity of MLL-edited CD34+ hematopoietic cells to initiate and recapitulate infant patients' features in pro-B-cell acute lymphoblastic leukemia (B-ALL). We provide key insights into the leukemogenic determinants of MLL-AF4+ infant B-ALL.

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A human genome editing-based MLL::AF4 ALL model recapitulates key cellular and molecular leukemogenic features

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A human genome editing-based MLL::AF4 ALL model recapitulates key cellular and molecular leukemogenic features

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